Data suitable for assembling a physiologically-based pharmacokinetic (PBPK) model for nanoparticles (NPs) remain relatively scarce. Therefore, there is a trend in extrapolating the results of in vitro and in silico studies to in vivo nanoparticle hazard and risk assessment. To evaluate the reliability of such approach, a pharmacokinetic study was performed using the same polyethylene glycol-coated gold nanoparticles (PEG-AuNPs) in vitro and in vivo. As in vitro models, human cell lines TH1, A549, Hep G2, and 16HBE were employed. The in vivo PEG-AuNP biodistribution was assessed in rats. The internalization and exclusion of PEG-AuNPs in vitro were modeled as first-order rate processes with the partition coefficient describing the equilibrium distribution. The pharmacokinetic parameters were obtained by fitting the model to the in vitro data and subsequently used for PBPK simulation in vivo. Notable differences were observed in the internalized amount of Au in individual cell lines compared to the corresponding tissues in vivo, with the highest found for renal TH1 cells and kidneys. The main reason for these discrepancies is the absence of natural barriers in the in vitro conditions. Therefore, caution should be exercised when extrapolating in vitro data to predict the in vivo NP burden and response to exposure.

The activity of submicron sized titanium oxide (TiO2) particles towards biomembrane models is coupled to their charge carrying capacity and their primary particle size. Electrochemical methods using a phospholipid layer on mercury (Hg) membrane model have been used to determine the phospholipid monolayer activity of TiO2 as an indicator of biomembrane activity. The particles were characterised for size, by dynamic light scattering (DLS) and scanning electron microscopy (SEM), and for charge, by acid-base titration. TiO2 nanoparticles aggregate in 0.1moldm(-3) solutions of KCl. The charge capacity of TiO2 nanoparticles depends on their primary particle size and is unaffected by aggregation. TiO2 particles of ∼40nm primary particle size interact significantly with phospholipid layers. Aggregation of these particles initially has a small effect on this interaction but long term aggregation influences the interaction whereby the aggregates penetrate the lipid layer rather than adsorbing on the surface. Fulvic acid does not inhibit the ∼40nm particle/phospholipid interaction. P25 TiO2 particles of larger particle size interact less strongly with phospholipid layers and the interaction is alleviated following particle aggregation. The semiconductor properties of TiO2 are evident in voltammograms showing electron transfer to TiO2 adsorbed on uncoated Hg.

We model cyclic voltammetry experiments on supported lipid films where a non-trivial dependence of the capacitance on the applied voltage is observed. Previously, based on a mean-field treatment of the Flory–Huggins type, under the assumption of strongly screened electrostatic interactions, it has been hypothesized that peaks in the capacitance-vs.-voltage profiles correspond to a sequence of structural or phase transitions within the adsorbed film. To examine this hypothesis, in this study we use both mean-field calculations and Monte Carlo simulations where the electrostatic effects due to the varying electric potential and the presence of salt are accounted for explicitly. Our main focus is on the structure of the film and the desorption–readsorption phenomena. These are found to be driven by a strong competition for the progressively charged-up (hydrophobic) surface between lipid hydrocarbon tails and the electrode counterions (cations). As the surface charge density is raised, the following phenomena within the interface are clearly observed: (i) a gradual displacement of the monolayer from the surface by the counterions, leading to complete monolayer desorption and formation of an electric double layer by the surface, (ii) a transformation of the monolayer into a bilayer upon its desorption, (iii) in the case of zwitterionic (or strongly polar) lipid head groups, the desorption is followed by the bilayer readsorption to the electrodevia interaction with the electric double layer and release of the excess counterions into the bulk solution. We argue then that the voltammetry peaks are associated with a stepwise process of formation of layers of alternating charge: electric double layer – upon film desorption, triple or multi-layer – upon film readsoption.